AB0264 ASSOCIATION BETWEEN DIFFERENT HLADRB1 ALLELES AND SEVERITY IN RHEUMATOID ARTHRITIS
Authors: M. Rojas-Giménez, J. Calvo Gutierrez, C. López-Medina, R. Ortega Castro, M. L. Ladehesa Pineda, A. Escudero Contreras
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To evaluate the association between different HLADRB1 alleles and the development of serious complications in patients with rheumatoid arthritis (RA). Methods We performed an observational, longitudinal and retrospective study of a cohort of 134 patients with established RA (ACR/EULAR 2010) from the registry of our department, older than 18 years and without other associated autoimmune pathologies except secondary Sjogren’s syndrome and who had the requested HLADRB1 genotype. Patients with ≥ 1 of the following HLA-DRB1 alleles were considered positive shared epitope carriers (SE+): *01:01, *01:02, *04:01, *04:04, *04:05, * 10:01, *03:01 or *07:01. The remaining patients without any of these alleles were considered shared epitope negative (SE-). Serious complications of RA were included: interstitial lung disease, cardiovascular events, cancer, admissions for serious infections, vasculitis, Felty’s syndrome, or death. Other severity data: erosions, rheumatoid nodules, multiple resistance to biologicals (3 or more biologicals), secondary Sjogren’s syndrome or osteoporosis. Descriptive and bivariate analysis was performed between the different alleles (χ 2 /ANOVA). Cox regression analysis was performed to estimate the influence of the different alleles on mortality. Results A total of 134 patients (91 SE+ and 43 SE-) were included. The main differences between the different alleles are shown in Table 1. The most frequent alleles were *0101 (n=18), *0301 (n=15) and *0701 (n=17). When the different alleles were compared, it was seen that the carriers of the alleles *04:05 presented positive ACPA more frequently (100%), rheumatoid nodules (50%) and showed higher mortality (50%) together with the carriers of *07:01 (41.2%), in a statistically significant way. There was no difference in the rest of the complications or severity data. The causes of death were varied in patients with both alleles (cardiovascular events, cancer, interstitial lung disease, and infections). There were no differences in age at death [mean 82.8 years (SD 3.8) vs 84.5 (6.6); p= 0.836, respectively]. Cox regression analysis adjusted for sex, age and ACPA showed that patients with alleles *04:05 (HR 9.1 (95% CI 1.1-72.3; p=0.036) and *07:01 (HR 10.9 (95% CI 1.5-81.2; p= 0.019) had a higher risk of mortality from any cause. Table 1. Characteristics of the patients with the different alleles Variables SE- (n= 43) *01:01 (n= 18) *01:02 (n= 10) *04:01 (n= 12) *04:04 (n=10) *04:05 (n= 4) *10:01 (n= 5) *03:01 (n= 15) *07:01 (n= 17) p Age at diagnosis (years), mean (SD) 54.1 (16.2) 48.5 (14.8) 55.5 (10.7) 45.7 (12.9) 50 (11.4) 56.8 (20.9) 55.1 (21.2) 50.5 (11.3) 59.7 (17.9) 0.336 Female sex, n (%) 30 (69.7) 12 (66.6) 7 (70) 10 (83.3) 9 (90) 0 3 (60) 12 (80) 12 (70.6) 0.096 Time since diagnosis (years), mean (SD) 12.8 (7.8) 15.3 (3.6) 11.8 (7.6) 14.1 (6) 11.03 (7.9) 9.3 (6.8) 11.8 (7.4) 16.4 (6.9) 12.3 (7.3) 0.420 RF +, n (%) 32 (74.4) 17 (94.4) 9 (90) 12 (100) 10 (100) 4 (100) 4 (80) 12 (80) 13 (76.5) 0.216 ACPA +, n (%) 27 (62.7) 16 (88.8) 9 (90) 11 (91.6) 10 (100) 4 (100) 5 (100) 9 (60) 8 (47) 0.004 Erosions, n (%) 12 (27.9) 9 (50) 3 (30) 8 (66.7) 5 (50) 2 (50) 2 (40) 7 (46.7) 7 (41.2) 0.422 Noduls, n (%) 0 1 (5.5) 0 1 (8.3) 1 (10) 2 (50) 1 (20) 0 1 (5.9) 0.003 Osteoporosis, n (%) 14 (32.5) 3 (16.7) 4 (40) 1 (8.3) 3 (30) 0 0 1 (6.6) 4 (23.5) 0.194 Sjogren S., n (%) 4 (9.3) 0 0 1 (8.3) 0 0 0 2 (13.3) 0 0.515 ILD, n (%) 5 (11.6) 1 (5.5) 1 (10) 2 (16.7) 2 (20) 0 0 2 (13.3) 2 (11.8) 0.937 CVD, n (%) 11 (25.6) 4 (22.2) 1 (10) 1 (8.3) 1 (10) 1 (25) 1 (20) 2 (13.3) 4 (23.5) 0.872 Serious infections, n (%) 11 (25.6) 1 (5.5) 1 (10) 0 2 (20) 2 (50) 0 2 (13.3) 2 (11.8) 0.646 Cancer, n (%) 4 (9.3) 3 (16.7) 1 (10) 1 (8.3) 2 (20) 1 (25) 1 (20) 2 (13.3) 2 (11.8) 0.972 Multiresistants, n (%) 2 (4.6) 2 (11.1) 0 1 0 1 0 2 0 0.465 Deaths, n (%) 12 (27.9) 2 (11.1) 0 0 0 2 (50) 0 1 (6.6) 7 (41.2) 0.005 Conclusion Our results suggest that RA patients carrying the *0405 and *0701 alleles have an increased risk of mortality. Studies with larger numbers of patients are needed to confirm these results. Disclosure of Interests None declared